MOA and Pharmacology
While the exact mechanism of action (MOA) of baclofen is not understood, it is clear that baclofen works by affecting monosynaptic and polysynaptic reflexes at the spinal level. Therefore, to be effective baclofen must be present within the cerebrospinal spinal fluid (CSF).1
When taking oral baclofen, a much larger dose is needed to have an effect because much of the medication does not make it to the CSF due to its low lipid solubility and poor ability to cross the blood-brain barrier.2-5 Lioresal® Intrathecal is administered directly into the CSF, so much less medication is needed to have an effect on spasticity.1
Lioresal® Intrathecal: The Benefit of Targeted Drug Delivery
With Lioresal® Intrathecal, there is 100 times less medication flowing through
your bloodstream than with oral baclofen.1
Even with lower dosages compared to oral baclofen, spasticity is significantly less frequent and less severe with ITB TherapySM with Lioresal® Intrathecal, as demonstrated in improvements in Modified Ashworth Scale (MAS) scores within 1 hour of therapy (maximal effect 2-4 hours) in 12 spasticity patients. Improvements increased with increasing dose (21% of patients noted improvements at 25 mcg, 50% at 50 mcg, and 57% at 75 mcg).6
MAS Scores After Continuous Dosing of Oral Baclofen and Bolus Dosing of ITB therapy7
Adapted from Reference 7: Heetla HW, Proost JH, Molmans BH, Staal MJ, van Laar T. A pharmacokinetic-pharmacodynamic model for intrathecal baclofen in patients with severe spasticity. Br J Clin Pharmacol. 2016;81(1):101-112.
An attempt should be made to discontinue concomitant oral antispasticity medication to avoid possible overdose or adverse drug interactions, either prior to screening or following implant and initiation of chronic Lioresal® Intrathecal infusion. Following pump implantation, and for each adjustment of the dosing rate of the pump and/or concentration of Lioresal® Intrathecal, the patient should be monitored closely until it is certain the patient’s response to the infusion is acceptable and reasonably stable.
- Lioresal® Intrathecal (baclofen injection) for intrathecal injection [prescribing information]. Saol Therapeutics, Roswell, Georgia; January 2019.
- KemstroTM (baclofen orally disintegrating tablets) for oral use [prescribing information]. Milwaukee, WI: Schwarz Pharma; Revised October 2003.
- Knutsson E, Lindblom U, Martensson A. Plasma and cerebrospinal fluid levels of baclofen (Lioresal®) at optimal therapeutic responses in spastic paresis. J Neurol Sci. 1974;23(3):473-484.
- Faigle JW, Keberle H. The chemistry and kinetics of Lioresal®. Postgrad Med J. 1972;48(Suppl 5):9-13.
- Muller H, Zierski J, Dralle D, Krauss D, Mutschler E. Pharmacokinetics of intrathecal baclofen. Local-spinal therapy of spasticity.1988:223-226.
- McCormick ZL, Chu SK, Binler D, et al. Intrathecal versus oral baclofen: a matched cohort study of spasticity, pain, sleep, fatigue, and quality of life. PM R. 2016;8(6):553-562.
- Heetla HW, Proost JH, Molmans BH, Staal MJ, van Laar T. A pharmacokinetic-pharmacodynamic model for intrathecal baclofen in patients with severe spasticity. Br J Clin Pharmacol. 2016;81(1):101-112.
- Albright AL. Baclofen in the treatment of cerebral palsy. J Child Neurol. 1996;11(2):77-83.
- Heetla HW, Staal MJ, Proost JH, van Laar T. Clinical relevance of pharmacological and physiological data in intrathecal baclofen therapy. Arch Phys Med Rehabil. 2014;95(11):2199-2206.
- Elovic E. Chapter 5: Assessment tools and treatment outcomes. In: Brashear A, Elovic E, eds. Spasticity: Diagnosis and Management. 2nd ed. New York, NY: Demos Medical Publishing, LLC, 2016.
- Francisco GE, Saulino M. Chapter 19: Intrathecal baclofen for spasticity. In: Brashear A, Elovic E, eds. Spasticity: Diagnosis and Management. 2nd ed. New York, NY: Demos Medical Publishing, LLC, 2016.